Plasma Protein Systems, Cytokines, and Inflammation Outcomes Flashcards
plasma protein systems
free floating proteins found in the blood, produced by the liver in a steady state during normal times, ramped up during inflammation; enzymatic cascades allow for amplification of immune response; all systems interact and also have regulatory components to turn it off
complement system
- triggered by 3 different pathways
- inflammation amplifier
- attacks pathogens
3 pathways of complement system
- classical pathway
- alternative pathway
- lectin pathway
classical pathway
- initiated by antigen:antibody complex
- activates C1 complex to start cascade
lectin pathway
- similar to classical pathway
- initiated by mannose-binding lectin (MBL)
alternative pathway
- initiated by pathogen antigens
- binds free-floating C3b to create C3 Convertase
complement cascade products
- C3a and C5a
- C3b
- C5b + C6-C9
C3a and C5a
- anaphylotoxins (cause mast cell degranulation)
- chemotactic factors (leaves trail for leukocytes to follow to where they’re needed)
C3b
opsonins (tags pathogen for removal)
C5b + C6-C9
membrane attack complex (MAC)
C3b attaches to _____; ___ recognize opsonins
bacteria surfaces; phagocytes
membrane attack complex (MAC)
complement proteins insert themselves into the membrane of pathogens, creating pores; water and ions enter the cell; cell swells and lyses
complement system deficiencies: activation disorders
hard time turning it on; recurrent infections
complement system deficiencies: inhibitory disorders
hard time turning it off; ex: hereditary angioedema
coagulation system is activated by ____
endothelial damage and bleeding
coagulation system: intrinsic pathway is triggered by ___
vascular damage and platelets
coagulation system: extrinsic pathway is triggered by ___
external damage and tissue factor
coagulation system: intrinsic and extrinsic pathways share ____
final pathway
coagulation system forms a ____, which ____
fibrinous meshwork; prevents hemorrhage, traps pathogens, and prepares for repair
coagulation system contributes to ____
inflammation (activates kinin and complement systems)
kinin system is activated by ____
bleeding
kinin system is ____
pro-inflammatory
product of kinin system is ____, which ____
bradykinin;
is similar to histamine; causes vasodilation, pain, smooth muscle contraction, increases vascular permeability, and leukocyte chemotaxis
cytokines are soluble factors produced by ____
cellular mediators of inflammation and injured cells
there are many types of cytokines, the 3 main ones we focused on are ____
interleukins, interferon, and tumor necrosis factor-a
cytokines are pleiotropic, meaning ___
the effect depends on which cells are activated; development, maturation, localization, and activation of immune cells
cytokines have ____ targets
local and distant
interleukins
- macrophage and lymphocyte product
- chemotactic
- activates adaptive immune response (i.e., lymphocytes)
- > 30 types
IL-1
endogenous pyrogen, chemotaxis, leukocytosis, pro-inflammatory
IL-10
inhibits lymphocyte growth and macrophage activity, anti-inflammatory
interferon
- produced by virus-infected cells, macrophages, and lymphocytes
- induces non-specific antiviral response and increases macrophage activity
tumor necrosis factor-a
- produced by macrophages and mast cells in response to PAMPs
- increases endothelial adhesion molecules and macrophage activity
short term effects of tumor necrosis factor-a
induces fever (endogenous pyrogen) and increases PPS (plasma protein system) production
long term effects of tumor necrosis factor-a
promotes cachexia (wasting) and intravascular thrombosis (clotting throughout body)
termination of inflammation
- removal of an offending agent usually ends response
- checks exist to control course of inflammation
checks exist to control course of inflammation:
- neutrophil lifespan is short
- inflammatory mediators degrade rapidly
- anti-inflammatory cytokines are also produced
4 outcomes of acute inflammation
1) complete resolution
2) scarring
3) abscess formation
4) progression to chronic formation
complete resolution
structure and function recoverable
scarring
substantial damage to connective tissue
abscess formation
pus confined in a closed space; active proteases produce a fluid, increasing pressure; usually must drain
progression to chronic inflammation
body cannot remove offending agent; persistent bacteria/toxins or autoimmune diseases
chronic inflammation
- inflammation lasting 2 weeks or longer
- often related to an unsuccessful acute inflammatory response
causes of chronic inflammation
- high lipid wax content of microorganism (tuberculosis)
- ability to survive inside the macrophage (chlamydia)
- toxins and chemical irritants (alcohol abuse)
- physical limitations (punctual plug)
- particulate matter (asbestos, soot, etc.)
chronic inflammation has a dense infiltration of ____
lymphocytes and macrophages (also fibroblasts)
chronic inflammation has fibrosis, which is ____
thickening and scarring of connective tissue (collagen)
chronic inflammation has angiogenesis, which is ____
production of new blood vessels (VEGF)
chronic inflammation has granuloma formation, which is ____
walling off of the offending agent with collagen